Synthesis of ketones

a column was prepacked with silica gel, and a solution of ethyl acetate-hexane (1 1) was dried over potassium carbonate. 

To a solution of ketone 7 (2.56 g, 10.5 mmol) and di-tert-butyl dicarbonate (2.75 g, 12.6 mmol) in freshly distilled tetrahydrofuran (32 mL) under nitrogen 

Hot hexanes-ether (3 1, 27 mL) was then added, and the suspension was allowed to stir without additional heating for 10 min. After filtration with suction, the suspension was washed with cold hexanes-ether (3 1, 20mL) to give the desired ketone 2 as a white solid (3.02 g, 84%). 

Extensive drying under a high vacuum removes the water of the hydrate to provide an uncomplicated NMR spectrum. 

One glass column, diameter 1 cm One magnetic stirrer plate 

Because addition of the acetylene to the aldehyde proved difficult after the introduction of the aminomethyl side chain, we decided to carry out this addition first, even though this generates a mixture of stereoisomers that has to be carried through several steps before they reconverge in the oxidation of alcohol 57 to ketone 58. This mixture is therefore of no consequence, although it complicates purification of the products and interpretation of the NMR spectra. 

Conversion of the diamine of 52 to a guanidine proved very challenging. Reaction of 52 with thiophosgene26 afforded cyclic thiourea 53 in only 40% yield and initial attempts to convert 53 to the guanidine were unsuccessful. Reaction with methyl iodide in MeOH at reflux afforded isothiourea 54, which did not form the desired guanidine on treatment with ammonia in MeOH. 

Presumably, reaction of chloride ion with benzyl chloroformate formed benzyl chloride. 

Bromination of ketone 58 could not be accomplished. The alcohol was therefore acetylated with acetic anhydride in pyridine at rt, which gave 87% of a 9 1 mixture of 59 and enol acetate 60. The enol acetate was the 

The stereochemistry of the newly formed six-membered ring of 63 was assigned based on the coupling constant, = 11.6 Hz, which is very 

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Addition to Carbonyl Compounds. Unlike Grignard and alkykitliium compounds, trialkylboranes are inert to carbonyl compounds. The air-catalyzed addition to formaldehyde is exceptional (373). Alkylborates are more reactive and can transfer alkyl groups to acyl halides. The reaction provides a highly chemoselective method for the synthesis of ketones (374). 

Hydroboration - regloseiective and stereoselective (syn) addition of BH3 (RBH2, R2BH) to olefins. Synthesis of alcohol including optically active alcohols from olefins. Also useful In synthesis of ketones by stitching ot olefins and CO... 

Synthesis of ketones Irom acids, acid chioildes, caitnnates via N-methoxyamides. 

The position of the keto group of A-homo-5a-cholestan-3-one (5b) was determined by Nelson and Schut by an unambiguous synthesis of ketone (5b) involving bis-homologation of 2,3-seco-5a-cholestane-2,3-dioic acid (8) using the Arndt-Eistert sequence [(9) (11)]. 

The (V-methyldihydrodithiazine 125 has also been used as an effective formyl anion equivalent for reaction with alkyl halides, aldehydes, and ketones (77JOC393). In this case there is exclusive alkylation between the two sulfur atoms, and hydrolysis to give the aldehyde products is considerably easier than for dithianes. However, attempts to achieve a second alkylation at C2 were unsuccessful, thus ruling out the use of this system as an acyl anion equivalent for synthesis of ketones. Despite this limitation, the compound has found some use in synthesis (82TL4995). 

The pinacol rearrangement reaction is of limited synthetic importance although it can be a useful alternative to the standard methods for synthesis of aldehydes and ketones." Especially in the synthesis of ketones with special substitution pattern—e.g. a spiro ketone like 5—the pinacol rearrangement demonstrates its synthetic potential ... 

The primary fate of acetyl CoA under normal metabolic conditions is degradation in the citric acid cycle to yield C02. When the body is stressed by prolonged starvation, however, acetyl CoA is converted into compounds called ketone bodies, which can be used by the brain as a temporary fuel. Fill in the missing information indicated by the four question marks in the following biochemical pathway for the synthesis of ketone bodies from acetyl CoA ... 

D. A. Shirley, The Synthesis of Ketones from Acidhalides and Organometallic Compounds of Magnesium, Zinc and Cadmium, Organic Rcaktions, Vol. VIII, 28 (1954). 

Polysubstituted 3-thiofiirans which are receiving a great interest as flavour and odour chemicals have been obtained by mono-//J5osubstitution and ortho-metallation from 3,4-dibromofuran <96T4065>. Dihydrofuran is used in a new synthesis of ketones from acids via acyl hemiacetals (Scheme 8, <96JOC6071>). 

Problem Suggest a synthesis of ketone (11), used in the manufacture of phentermine, a drug used to control obesity. 

Adipose tissue releases free fatty acids in statvation, and these ate used by many tissues as fuel. Futthet-mote, in the hvet they ate the substtate fot synthesis of ketone bodies. 

Pioneering work on the desulphonylation of jS-ketosulphones was carried out by Corey and Chaykovsky - . This reaction was part of a sequence which could be used in the synthesis of ketones, as shown in equation (53). The main thrust of this work was in the use of sulphoxides, but Corey did stress the merits of both sulphones and sulphonamides for different applications of this type of reaction. The method soon found application by Stetter and Hesse for the synthesis of 3-methyl-2,4-dioxa-adamantane , and by House and Larson in an ingenious synthesis of intermediates directed towards the gibberellin skeleton, and also for more standard applications . Other applications of the method have also been madealthough it does suffer from certain limitations in that further alkylation of an a-alkyl- -ketosulphone is a very sluggish, inefficient process. Kurth and O Brien have proposed an alternative, one-pot sequence of reactions (equation 54), carried out at — 78 to — 50°, with yields better than 50%. The major difference between the two routes is that the one-pot process uses the desulphonylation step to generate the enolate anion, whereas in the Corey-House procedure, the desulphonylation with aluminium amalgam is a separate, non-productive step. 

Examples of this approach to the synthesis of ketones and carboxylic acids are presented in Scheme 1.4. In these procedures, an ester group is removed by hydrolysis and decarboxylation after the alkylation step. The malonate and acetoacetate carbanions are the synthetic equivalents of the simpler carbanions that lack the additional ester substituent. 

One reaction that is quite efficient for lithium reagents but poor for Grignard reagents is the synthesis of ketones from carboxylic acids.112 The success of the... 

Organopalladium intermediates are also involved in the synthesis of ketones and other carbonyl compounds. These reactions involve acylpalladium intermediates, which can be made from acyl halides or by reaction of an organopalladium species with carbon monoxide. A second organic group, usually arising from any organometallic reagent, can then form a ketone. Alternatively, the acylpalladium intermediate may react with nucleophilic solvents such as alcohols to form esters. 

Procedures for the synthesis of ketones based on coupling of organostannanes with acyl halides have also been developed.211 The catalytic cycle is similar to that involved in coupling with aryl halides. The scope of compounds to which the reaction is applicable includes tetra-u-butylstannane. This example indicates that the reductive elimination step competes successfully with (3-elimination. 

Scheme 8.13. Synthesis of Ketones from Acyl Chlorides and Stannanes...

Scheme 8.15. Synthesis of Ketones, Esters, Carboxylic Acids, and Amides by Palladium-Catalyzed Carbonylation and Acylation... 

Section B of the Scheme 9.1 shows several procedures for the synthesis of ketones. Entry 6 is the synthesis of a symmetrical ketone by carbonylation. Entry 7 illustrates the synthesis of an unsymmetrical ketone by the thexylborane method and also demonstrates the use of a functionalized olefin. Entries 8 to 10 illustrate synthesis of ketones by the cyanide-TFAA method. Entry 11 shows the synthesis of a bicyclic ketone involving intramolecular hydroboration of 1,5-cyclooctadiene. Entry 12 is another ring closure, generating a potential steroid precursor. 

Other bonds that merit attention are those connecting C(7) through C(ll). These could be formed by one of the many methods for the synthesis of ketones. Bond disconnections at carbonyl centers can involve the 0=C-C(a) (acylation, organometallic addition), the C(a)-C((3) bond (enolate alkylation, aldol addition), or C((3)-C(7) bond (conjugate addition to enone). 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

The intermolecular Heck reaction of halopyridines provides an alternative route to functionalized pyridines, circumventing the functional group compatibility problems encountered in other methods. 3-Bromopyridine has often been used as a substrate for the Heck reaction [124-126]. For example, ketone 155 was obtained from the Heck reaction of 3-bromo-2-methoxy-5-chloropyridine (153) with allylic alcohol 154 [125]. The mechanism for such a synthetically useful coupling warrants additional comments oxidative addition of 3-bromopyridine 153 to Pd(0) proceeds as usual to give the palladium intermediate 156. Subsequent insertion of allylic alcohol 154 to 156 gives intermediate 157. Reductive elimination of 157 gives enol 158, which then isomerizes to afford ketone 155 as the ultimate product This tactic is frequently used in the synthesis of ketones from allylic alcohols. 

Whereas the first reaction, which results in the synthesis of ketones, is much used because of the ease with which it usually proceeds, the introduction of alkyl groups proves much less satisfactory since, in the first place, the substitution goes further and, in the second, the alkyl groups may at the same time be partially split off again. The method of Fittig is usually to be preferred in this case. 

The direct synthesis of ketones from hydrocarbons and phosgene, e.g. 

One-Pot Multistep Synthesis of Ketones on Bifunctional Zeolite Catalysts. One-pot multistep reactions constitute an elegant and efficient way to decrease the number of chemical and separation steps, hence, to develop greener synthesis processes. Bifunctional metal-acidic or metal-basic zeolite catalysts, which can be prepared easily with the desired properties (e.g., distribution of the... 

The reaction between zinc-copper reagents and acid chlorides is very general and provides a useful synthesis of ketones [7, 34, 41, 42], This acylation has also been used to prepare various indoles substituted in position 2 (Scheme 2.42) [88],... 

However, oxidation processes like epoxidation or dihydroxylation reactions are important transformations in solid support chemistry, because they allow the synthesis of ketones [226], aldehydes [227, 228] and even sulfoxides and sulfones [229]. 

Acetyl-CoA, from P-oxidation, is the immediate substrate for synthesis of ketone bodies, which is achieved in four reactions as follows ... 

Figure 7.16 Pathway for the synthesis of ketone bodies the HMG-CoA pathway.

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